Accelerated immune ageing is associated with COVID-19 disease severity

Medientyp: E-Artikel
Titel: Accelerated immune ageing is associated with COVID-19 disease severity
Beteiligte: Lord, Janet M.; Veenith, Tonny; Sullivan, Jack; Sharma-Oates, Archana; Richter, Alex G.; Greening, Neil J.; McAuley, Hamish J. C.; Evans, Rachael A.; Moss, Paul; Moore, Shona C.; Turtle, Lance; Gautam, Nandan; Gilani, Ahmed; Bajaj, Manan; Wain, Louise V.; Brightling, Christopher; Raman, Betty; Marks, Michael; Singapuri, Amisha; Elneima, Omer; Openshaw, Peter J. M.; Duggal, Niharika A.; Abel, K.; Adamali, H.; [...]
Erschienen: Springer Science and Business Media LLC, 2024
Erschienen in: Immunity & Ageing
Sprache: Englisch
DOI: 10.1186/s12979-023-00406-z
ISSN: 1742-4933
Schlagwörter: Aging ; Immunology
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Beschreibung: <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe (<jats:italic>n</jats:italic> = 56; age 53.12 ± 11.30 years), moderate (<jats:italic>n</jats:italic> = 32; age 52.28 ± 11.43 years) or mild (<jats:italic>n</jats:italic> = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (<jats:italic>n</jats:italic> = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (<jats:italic>p</jats:italic> < 0.0001); increased frequency of EMRA CD4 (<jats:italic>p</jats:italic> < 0.003) and CD8 T cells (<jats:italic>p</jats:italic> < 0.001); a higher frequency (<jats:italic>p</jats:italic> < 0.0001) and absolute numbers (<jats:italic>p</jats:italic> < 0.001) of CD28<jats:sup>−ve</jats:sup> CD57<jats:sup>+ve</jats:sup> senescent CD4 and CD8 T cells; higher frequency (<jats:italic>p</jats:italic> < 0.003) and absolute numbers (<jats:italic>p</jats:italic> < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (<jats:italic>p</jats:italic> < 0.0001); higher frequency of memory B cells (<jats:italic>p</jats:italic> < 0.001) and increased frequency (<jats:italic>p</jats:italic> < 0.0001) and numbers (<jats:italic>p</jats:italic> < 0.001) of CD57<jats:sup>+ve</jats:sup> senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (<jats:italic>p</jats:italic> < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity (<jats:inline-formula><jats:alternatives><jats:tex-math>$$\beta$$</jats:tex-math><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mi>β</mml:mi> </mml:math></jats:alternatives></jats:inline-formula> = 0.174, <jats:italic>p</jats:italic> = 0.043), with a major influence being disease severity (<jats:inline-formula><jats:alternatives><jats:tex-math>$$\beta$$</jats:tex-math><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mi>β</mml:mi> </mml:math></jats:alternatives></jats:inline-formula> = 0.188, <jats:italic>p</jats:italic> = 0.01). </jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease. </jats:p> </jats:sec>
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